SRPRA

protein-coding

SRP receptor subunit alpha

Gene summary

The gene encodes a subunit of the endoplasmic reticulum signal recognition particle receptor that, in conjunction with the signal recognition particle, is involved in the targeting and translocation of signal sequence tagged secretory and membrane proteins across the endoplasmic reticulum. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2010]

Previous symbols:

SRPR

MANE transcript

NM_003139.4

Inheritance

ClinVar variants

P:1U:27B:9

Top phenotype

SRPRA-related disorder

gnomAD constraint

pLI —, LoF o/e 0.19

Max pathogenic AF

—

Genomic locus

chr11:126,262,938-126,269,144

External References & Databases

Ensembl (ENSG00000182934)

Transcript & Mutation Effects

hg38 • Region Span ~6.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Shwachman-Diamond syndromeMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0009833

Submitter: PanelApp Australia

complex neurodevelopmental disorderLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0100038

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SRPRA variants in ClinVar

6 Conditions Cataloged

SRPRA-related disorderTotal: 15

not providedTotal: 8

not specifiedTotal: 5

Shwachman-Diamond syndrome 1Total: 1

Severe congenital neutropeniaTotal: 1

See casesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003139.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	7 clinvar		8
missense	1 clinvar		19 clinvar	1 clinvar	1 clinvar	22
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			7 clinvar			7
Total	1	0	27	8	1	37

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 21 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003139.4	RefSeq	NP_003130.2	14	MANE Select
ENST00000332118.11	Ensembl	ENSP00000328023.5	14	MANE Select
NM_001177842.2	RefSeq	NP_001171313.1	13	Standard
ENST00000532259.1	Ensembl	ENSP00000435508.1	13	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Protein export - Homo sapiens (human)
XBP1(S) activates chaperone genes
SRP-dependent cotranslational protein targeting to membrane
Translation
Metabolism of proteins

Biological Process

protein targeting
cotranslational protein targeting to membrane
SRP-dependent cotranslational protein targeting to membrane
IRE1-mediated unfolded protein response
protein targeting to ER

Molecular Function

RNA binding
GTPase activity
signal recognition particle binding
GTP binding

Cellular Component

signal recognition particle receptor complex
endoplasmic reticulum membrane
membrane
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000332118
Coding exons: 14
Length: 6226
Individuals with no LoFs: 125725
Homozygous LoFs: 0
Heterozygous LoFs: 23
Defined: 125748
p: 0.0000915

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.17	329	394	0.835	0.0000236	4194
Missense (PolyPhen)		125	183.72	0.68039		1923
Synonymous	-0.681	151	141	1.07	0.00000766	1271
Loss of Function	3.92	5	27.0	0.185	0.00000121	342

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00020	0.00020	rare
Ashkenazi Jewish	0.00040	0.00040	rare
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000088	0.000088	rare
South Asian	0.000065	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Component of the SRP (signal recognition particle) receptor. Ensures, in conjunction with the signal recognition particle, the correct targeting of the nascent secretory proteins to the endoplasmic reticulum membrane system.;

Recessive Scores

pRec: 0.160

Intolerance Scores

RVIS EVS: -0.89
RVIS percentile EVS: 10.43

Essentials

Essential (gene trap): E